Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003534696 | SCV000830717 | uncertain significance | Familial adenomatous polyposis 1 | 2020-10-15 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with APC-related disease. This variant is present in population databases (rs765104249, ExAC 0.002%). This sequence change replaces isoleucine with valine at codon 1975 of the APC protein (p.Ile1975Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. |
Color Diagnostics, |
RCV000775336 | SCV000909607 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-01 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 1975 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250632 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV000775336 | SCV001186749 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-07 | criteria provided, single submitter | clinical testing | The p.I1975V variant (also known as c.5923A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 5923. The isoleucine at codon 1975 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |